Sensory neurones provides a convenient model system to study the chemosensitivity and ionic conductance mechanisms of a number of neurotransmitters particularly in relation to their potential effects in controlling the excitability of afferent nerve terminals. A portion of small diameter dorsal root ganglion cells and their axons contains substance P and this undecapeptide has been implicated in transmission of noxious information. This proposal seeks to pursue the actions of substance P on sensory neurones and this promise to provide evidence for a multiplicity of actions of physiological and pharmacological importance. Microphysiological methods involving intracellular recording and extracellular drug administration would be used in a series of related in vivo and in vitro experiments directed towards (1) characterizing the properties of rat DRG cells maintained in vitro in terms of their action potential generation, membrance ionic conductances, and axonal conduction velocity; (2) studying the biophysical effects of substance P administered in the bathing medium or directly to the somatic membrance of characterized cells, particularly small cells with slow conducting axons; (3) evaluating the ionic dependency of the substance P effect and particularly its action on membrane potassium or calcium permeability; (4) functionally identifying DRG cells which respond to substance P in terms of their sensory modalities determined in vivo by exploring the peripheral receptive field properties in the anesthetized cat. Particular attention would be devoted to identification of cells responding to noxious stimulation; (5) studying pharmacological interactions of substance P with other neurotransmitters, for example, serotonin, opioid peptides to seek evidence for a functional relationship and to further explore postulated actions related to drug effects, for example, baclofen, opiate analgesics. Information would be acquired concerning the properties of smaller cells with slow conducting fibers since this cell group is of unique functional significance especially in relation to transmission of sensory modality such as pain and to the actions of substance P. These findings would have signficant implication for its role in central neurotransmission and provide information concerning a role in the ganglion itself. Finally, the study of pharmacological interactions would provide information on the mechanism of action of important classes of drugs.